Search Results (896)

Background: Pharmacovigilance systems have flagged possible associations between mRNA COVID-19 vaccination and systemic autoimmune inflammatory rheumatic diseases (AIRDs), generating uncertainty for rheumatologists counselling patients. As the first population-scale deployment of an mRNA vaccine platform, COVID-19 vaccination provides a unique setting to examine whether autoimmune safety signals detected in spontaneous reporting systems correspond to measurable disease risk. We synthesised pharmacovigilance and population-based evidence on incident EULAR-defined systemic AIRDs after mRNA COVID-19 vaccination and assessed whether disproportionality signals were corroborated by analytical studies. Methods: We conducted a PRISMA 2020-compliant systematic review searching MEDLINE, Web of Science, Scopus, Embase, and the Cochrane Library from 2019 to April 2026, supplemented by medRxiv and trial registries. Eligible studies included pharmacovigilance disproportionality analyses and analytical studies, including cohorts and randomised controlled trials, evaluating BNT162b2 or mRNA-1273 in adults without known pre-existing autoimmune disease. Risk of bias was assessed using READUS-PV, ROBINS-I, and RoB 2. Meta-analysis was not performed because of substantial heterogeneity. Results: Fourteen studies were included: seven pharmacovigilance studies and seven analytical studies. Disproportionality analyses suggested increased reporting of selected AIRDs, most consistently polymyalgia rheumatica and giant cell arteritis, mainly when all other adverse-event reports served as comparators. These signals were largely neutral when influenza vaccines were the reference. Across analytical studies, associations were inconsistent; modest increases in systemic lupus erythematosus appeared only in selected analyses. Long-term evidence was scarce: only four studies, from three countries (South Korea, Israel, and Norway), followed participants for up to approximately one year, and three of these reported at least one positive association—systemic lupus erythematosus, post-booster rheumatoid arthritis, and polymyalgia rheumatica in older adults—whereas studies restricted to risk windows of three months or less reported no increase. Conclusions: The available evidence does not indicate a consistent increase in incident systemic AIRDs after mRNA COVID-19 vaccination. Although pharmacovigilance studies identified comparator-dependent signals for selected diseases, particularly polymyalgia rheumatica and giant cell arteritis, these findings were generally not confirmed in comparative population-based studies and should be considered hypothesis-generating. Delayed-onset disease remains poorly characterised, and studies with at least one year of follow-up are needed. Full article

Background/Objectives: Vaccination remains an important means of protection against influenza and COVID-19. Administering influenza and COVID-19 vaccines as a combined formulation may be advantageous. Methods: This phase 3, randomized study evaluated an investigational combination nucleoside-modified messenger RNA (modRNA) vaccine formulated with monovalent XBB.1.5-adapted BNT162b2 vaccine (BNT162b2) and an investigational influenza modRNA vaccine (hereafter investigational combination modRNA vaccine); we report safety, tolerability, and immunogenicity of the investigational combination modRNA vaccine in healthy 18- to 64-year-olds in two cohorts (2 and 3). Results: In Cohort 2, 3127 participants received the investigational combination modRNA vaccine and 1563 received the concomitant licensed quadrivalent influenza vaccine (QIV) with BNT162b2. In Cohort 3, 1189 participants received the investigational combination modRNA vaccine, 605 received QIV, 607 received the investigational influenza modRNA vaccine, and 1191 received BNT162b2. Prespecified noninferiority criteria of the geometric mean ratio of strain-specific hemagglutination inhibition (HAI) or SARS-CoV-2 Omicron XBB.1.5 neutralizing titers or differences in percentages of participants achieving HAI sero-conversion or Omicron XBB.1.5 seroresponse for investigational combination modRNA vaccine to concomitant QIV and BNT162b2 (or to QIV and BNT162b2 each administered alone in Cohort 3) were met for influenza A and SARS-CoV-2 Omicron XBB.1.5 strains but not for the influenza B strain. The investigational combination modRNA vaccine was well tolerated with an acceptable safety profile. Conclusions: The single-dose investigational combination influenza plus COVID-19 modRNA vaccine elicited robust immune responses against influenza A and SARS-CoV-2 with acceptable safety. Further work is required to optimize influenza B responses. The modRNA platform offers promise and potential advantages for vaccine development. ClinicalTrials.gov Identifier: NCT06178991 (approval date: 20 December 2023). Full article

Background and Clinical Significance: The COVID-19 pandemic led to the rapid development of effective vaccination strategies. Although COVID-19 vaccines are generally safe, rare hematological adverse events have been reported, most prominently vaccine-induced immune thrombotic thrombocytopenia (VITT). Isolated cases of autoimmune cytopenias and bone marrow failure syndromes following COVID-19 vaccination have also been described. Case Presentation: We report the case of an 80-year-old male who developed subacute-onset severe normocytic anemia with reticulocytopenia and mild leukopenia following heterologous COVID-19 vaccination with ChAdOx1 nCoV-19 (AstraZeneca) and BNT162b2 (Pfizer–BioNTech). Seven days after the second vaccination, mild anemia was detected, progressing over the following weeks to symptomatic anemia requiring hospitalization. Extensive diagnostic evaluation revealed no evidence of hemolysis, nutritional deficiency, autoimmune disease, or viral infection, including SARS-CoV-2 and Parvovirus B19. Bone marrow examination demonstrated an erythroid maturation arrest at the proerythroblast stage, resembling a pure red cell aplasia (PRCA)-like pattern. Cytogenetic and molecular analyses excluded myelodysplastic syndromes. Treatment with erythropoietin resulted in complete hematologic recovery. Conclusions: This case suggests that, in rare instances, COVID-19 vaccination may be temporally associated with transient suppression of erythropoiesis. Further studies are required to elucidate underlying mechanisms and to guide diagnosis and management. Full article

Background/Objectives: Waning immunity after primary COVID-19 vaccination supports evaluation of additional doses. HXP-GPOVac is an egg-based, inactivated Newcastle disease virus (NDV)-vectored vaccine expressing a prefusion-stabilized SARS-CoV-2 HexaPro spike antigen. We evaluated the safety, tolerability, and immunogenicity of a single additional 10 µg dose of HXP-GPOVac administered to adults previously primed with two doses of either HXP-GPOVac or BNT162b2. Methods: Study GPO NDV-HXP-S 203 was an open-label phase II extension enrolling adults (18–75 years) who previously completed a two-dose primary series in Study 202 with either HXP-GPOVac or BNT162b2 (Pfizer–BioNTech; Comirnaty). All participants received a single additional 10 µg intramuscular dose of HXP-GPOVac ≥ 6 months after their second primary dose. Solicited local/systemic adverse events (AEs) were recorded for 7 days, unsolicited AEs through Day 28, and serious AEs (SAEs) and adverse events of special interest (AESIs) throughout follow-up. Neutralizing antibody titers (pseudovirus 50% neutralization titer, NT₅₀) and anti-spike IgG (BAU/mL) were assessed pre-dose (Day 1) and post-vaccination through 12 months; a predefined subset underwent IFN-γ and IL-5 ELISpot. SARS-CoV-2 infection during follow-up was assessed using anti-nucleocapsid (anti-N) IgG. Symptomatic COVID-19 was identified through symptom-reported, symptom-triggered RT-PCR testing; sequencing was performed when feasible. Results: All 219 participants received HXP-GPOVac (167 primed with HXP-GPOVac and 52 with BNT162b2). Any solicited local reaction occurred in 22.2% (37/167) of HXP-GPOVac-primed and 26.9% (14/52) of BNT162b2-primed participants; any solicited systemic reaction occurred in 10.8% (18/167) and 13.5% (7/52), respectively. No vaccine-related unsolicited AEs or AESIs were reported. Three deaths occurred during the 12-month follow-up; one (a sudden cardiac death in an HXP-GPOVac-primed participant) was assessed by the safety medical team as possibly related to vaccination, and two were assessed as not related. Neutralizing antibody GMTs increased from 46.33 at baseline to 1569.04 at Day 15 in HXP-GPOVac-primed participants and from 77.25 to 841.34 in BNT162b2-primed participants; corresponding SCRs were 78.8% and 76.9%. Anti-spike IgG GMCs increased from 48.79 to 1480.14 BAU/mL and from 194.48 to 1547.88 BAU/mL, respectively. Responses declined over time but remained above baseline through 12 months. In the cellular immunity subset, post-vaccination IFN-γ responses increased, with comparatively modest IL-5 responses and no pattern suggestive of Th2 predominance. Conclusions: A single additional dose of HXP-GPOVac administered ≥6 months after primary vaccination with HXP-GPOVac or BNT162b2 was generally well tolerated and elicited robust recall humoral responses, with supportive findings of cellular immunity. Trial registration: Thai Clinical Trials Registry, TCTR20230213001. Full article

Background: The BNT162b2 vaccine is safe and effective for COVID-19 prevention. BNT162b2 safety and immunogenicity have been evaluated in immunocompromised individuals in real-world observational studies, particularly in pediatric populations, but not in clinical trials. Methods: This phase 2b single-arm trial descriptively evaluated a Dose 3 (age-appropriate) BNT162b2 primary series with a Dose 4 in immunocompromised individuals 2–<5, 5−<12, 12–<18, and ≥18 years of age without a previous clinical or microbiological COVID-19 diagnosis. Primary objectives were to describe immune responses, reactogenicity, and adverse events following vaccination. Results: Out of 124 participants enrolled, 119 received Dose 3 and 90 received Dose 4. Among participants without evidence of past SARS-CoV-2 infection, neutralizing geometric mean titers (GMTs) and geometric mean fold rises (GMFRs) against the SARS-CoV-2 ancestral strain ranged from 344.6 to 1584.4 and 7.9 to 36.4 at 1 month after Dose 3 and from 1474.0 to 4157.9 and 31.0 to 95.6 at 1 month after Dose 4, respectively, across age groups. Among participants with or without evidence of past infection, GMTs and GMFRs ranged from 787.1 to 2940.6 and 9.6 to 54.3 at 1 month after Dose 3 and from 1031.3 to 13,457.1 and 9.1 to 220.0 at 1 month after Dose 4. Percentages of participants with or without evidence of past SARS-CoV-2 infection achieving seroresponse ranged from 50.0 to 92.9% at 1 month after Dose 3, and from 75.0 to 100% and 33.3 to 100.0% at 1 and 6 months after Dose 4 across age groups, respectively. No new safety signals were identified. Conclusions: BNT162b2 was immunogenic, increasing GMTs in immunocompromised individuals ≥2 years old, particularly after Doses 3 and 4. GMT increases were generally similar across age groups and disease subsets. Three or four BNT162b2 doses had a favorable risk-benefit profile in this population. Full article

Background: The dynamics of humoral immune responses following primary and booster COVID-19 vaccinations are crucial to understand in order to optimize vaccination strategies. This study evaluates the magnitude and durability of SARS-CoV-2-specific IgG antibody responses across different vaccines in a large cohort of Bangladeshi adults. Methods: A total of 6300 adults from nine hospitals across eight divisions of Bangladesh were enrolled. Participants received two primary doses of either ChAdOx1 nCoV-19 (Covishield, Serum Institute of India, n = 2855), mRNA-1273 (Moderna, n = 578), BNT162b2 (Pfizer-BioNTech, n = 121), or Vero-cell-inactivated (Sinopharm, n = 2746) vaccines. Booster doses were administered at one-year intervals post-primary vaccination. SARS-CoV-2 spike receptor-binding domain (RBD)-specific IgG antibody responses were measured by ELISA using serum from vaccinees at multiple time points after two primary and two booster doses. Results: A total of 3745 individuals received booster 1 (third dose), with 59% receiving heterologous boosters (a different vaccine regimen than the primary doses). Only 5.5% (n = 347) of participants received a second booster one year after the first booster (among them, 99% received BNT162b2). Our results suggest that heterologous boosters with the mRNA vaccine induced higher IgG levels than homologous boosters for individuals who received primary vaccination with adenovirus vector-based ChAdOx1 nCoV-19 or a Vero-cell-inactivated vaccine. However, in those who initially received the mRNA-based vaccine, both homologous and heterologous boosters produced comparable IgG responses. Among all vaccine types, booster immunization with the Vero-cell-inactivated vaccine induced the lowest antibody responses. Longitudinal analysis demonstrated significantly high IgG levels over the 12 months following the first booster (p < 0.0001); however, IgG levels declined significantly after the second booster dose (fourth dose). Conclusions: Heterologous boosting strategies, particularly those involving mRNA vaccines, elicit stronger and more sustained IgG responses compared to a homologous booster. However, antibody waning after the second booster highlights the need for continued monitoring and potential additional vaccine strategies. Full article

Background/Objectives: HXP-GPOVac is a locally produced, inactivated Newcastle disease virus-based (NDV-HXP-S) COVID-19 vaccine manufactured in Thailand. This phase II trial compared its safety and immunogenicity with the mRNA vaccine BNT162b2 in adults aged 18–75 years. Methods: In this randomized, double-blind, active-controlled trial registered with the Thai Clinical Trials Registry (TCTR20220819003), 300 participants were assigned 3:1 to receive HXP-GPOVac or BNT162b2 on Days 1 and 29. Solicited adverse events (AEs) were recorded for 7 days after each dose, AEs were summarized through 28 days after each dose, and serious adverse events (SAEs), medically attended AEs (MAAEs), and adverse events of special interest (AESIs) were collected through Day 197. Humoral immunogenicity was assessed by pseudovirus 50% neutralization titers (NT₅₀) and anti-spike IgG concentrations at baseline, Day 29, Day 43, and Day 197. Seroconversion was defined as a ≥4-fold increase from baseline. A predefined subset underwent interferon-γ (IFN-γ) and interleukin-5 (IL-5) ELISpot assays to assess cell-mediated immune responses. The primary immunogenicity analysis assessed non-inferiority of HXP-GPOVac compared with BNT162b2 based on the NT₅₀ geometric mean titer ratio, with a prespecified non-inferiority margin of 0.5. Results: Solicited AEs were predominantly mild and occurred more frequently after the first dose in both groups; one or more solicited local or systemic AEs were reported by 23.7% (95% CI: 18.3–29.8) of HXP-GPOVac recipients and 44.7% (95% CI: 33.3–56.6) of BNT162b2 recipients after the first dose. AEs through 28 days after vaccination and SAEs were uncommon; MAAEs occurred in 17.0% of HXP-GPOVac recipients and 22.4% of BNT162b2 recipients, and none were considered related to vaccination. In the HXP-GPOVac group, NT₅₀ geometric mean titers increased from 5.6 at baseline to 65.5 at Day 29 and 505 at Day 43, declining to 63.6 at Day 197. Anti-spike IgG geometric mean concentrations rose from 7.5 BAU/mL at baseline to 102.7 BAU/mL at Day 29 and 514.6 BAU/mL at Day 43, decreasing to 61.0 BAU/mL at Day 197. BNT162b2 induced higher antibody levels at all time points. The NT₅₀ GMT ratio (HXP-GPOVac/BNT162b2) at Day 43 was 0.51 (95% CI: 0.39–0.67); the lower bound did not exceed the prespecified non-inferiority margin of 0.5, and non-inferiority was not established. Seroconversion rates at Day 43 were 97.6% for HXP-GPOVac and 97.1% for BNT162b2 (neutralizing antibody) and 98.6% and 97.1%, respectively (anti-spike IgG). ELISpot analyses demonstrated increased IFN-γ responses after the second dose without evidence of Th2-dominant skewing. Conclusions: HXP-GPOVac was well tolerated and induced substantial humoral and cellular immune responses, with high seroconversion rates and balanced T-cell polarization. Although absolute antibody levels were lower than those induced by BNT162b2 and the prespecified non-inferiority criterion was not met, these findings support continued evaluation of the inactivated NDV-HXP-S vaccine platform. Full article

mRNA vaccines are a relevant approach in cancer immunotherapy, using messenger RNA to induce immune responses against tumor-associated antigens. In this review, BNT111 and BNT122 are compared as representative off-the-shelf and personalized models. BNT111 is a fixed mRNA vaccine that has demonstrated significant antitumor efficacy against shared melanoma antigens, particularly when combined with immune checkpoint inhibitors. It allows a standardized production via in vitro transcription (IVT) in a cell-free system. Conversely, BNT122 is a personalized vaccine designed to match an individual’s tumor mutations by targeting patient-specific neoantigens to elicit more robust immune responses. It has significant suitability in the adjuvant setting to target minimal residual disease. Despite favorable safety and immunogenicity, the effectiveness of these vaccines is influenced by various factors, including tumor heterogeneity, differences in antigen expression, off-target effects on mRNA-LNP distribution, molecular instability, and complex manufacturing constraints. Neither approach can be directly considered as the definitive optimal vaccine. A comprehensive analysis of their strengths and limitations is vital for a balanced and objective future research direction. Collectively, this emphasizes the need for further improvements in vaccine design and strategies, prioritizing high-quality, safe, and accessible treatments for every cancer-based patient and ensuring their successful integration into healthcare. Full article

Background: COVID-19 remains a substantial public health challenge in the Netherlands. Next-generation COVID-19 vaccine, mRNA-1283, is approved in the European Union, with potential for higher relative vaccine efficacy compared with originally licensed COVID-19 vaccines. Methods: The potential public health and economic impact of mRNA-1283 in adults ≥ 60 years and high-risk adults aged 18–59 years was modeled versus no vaccination and originally licensed mRNA-1273 and BNT162b2, adapting a published static Markov model with a 1-year time horizon. COVID-19 burden reflected two full post-pandemic seasons. Vaccine efficacy versus mRNA-1273 was based on pivotal phase 3 NextCOVE trial data; efficacy versus BNT162b2 was derived from an indirect treatment comparison. The economically justifiable price (EJP) of mRNA-1283 versus no vaccination and price premiums over existing vaccines were determined at a willingness-to-pay threshold of €50,000/quality-adjusted life-year (QALY) gained. Results: Without COVID-19 vaccination, an estimated 460,000 infections, 23,800 hospitalizations, and 5300 deaths would occur. With current coverage, mRNA-1283 was estimated to prevent 68,000 infections, 5400 hospitalizations, and 1200 deaths, saving 9667 QALYs and over €66.5 million in treatment costs. The EJP was €238 versus no vaccination. Compared with mRNA-1273 and BNT162b2, mRNA-1283 was estimated to prevent additional burden (e.g., 1309 and 1679 hospitalizations, respectively) and was cost-effective at an incremental EJP of €62 versus mRNA-1273 and €80 versus BNT162b2. Conclusions: The results support continued COVID-19 vaccination to mitigate the ongoing health and societal burden of SARS-CoV-2 in the Netherlands. The comparative analyses indicate that mRNA-1283 may be associated with substantial health benefits over originally licensed mRNA vaccines; consequently, its use may further improve health outcomes and economic efficiency within COVID-19 vaccination programs. Full article

People with HIV (PWH) may exhibit altered immune responses to SARS-CoV-2 vaccination due to persistent immune dysregulation despite antiretroviral therapy. We evaluated humoral immunogenicity following mRNA SARS-CoV-2 vaccination in PWH according to CD4 T-cell count and compared responses with HIV-negative controls. The study included 57 PWH stratified by CD4 count (<200 and ≥200 cells/µL), alongside 12 HIV-negative controls. Neutralizing antibody titers (NT50) against SARS-CoV-2 pseudoviruses expressing the D614G and Omicron BA.5 spike variants were measured using a luciferase-based neutralization assay one month (M1) and six months (M6) after primary vaccination with BNT162b2 or mRNA-1273. PWH with CD4 counts ≥ 200 cells/µL demonstrated higher neutralizing titers against D614G at M1 and M6, with significant differences observed between CD4 groups (M1: p = 0.03; M6: p = 0.02). Neutralization of BA.5 was lower overall; while no overall group differences were observed at M1, higher titers were detected among individuals with CD4 ≥ 200 cells/µL at six months (p = 0.04). Neutralizing titers correlated positively with CD4 counts among PWH. Responses were broadly comparable between PWH and HIV-negative controls and did not differ substantially by vaccine type. These findings indicate that immune status, reflected by CD4 T-cell count, is a key determinant of SARS-CoV-2 vaccine-induced humoral responses in PWH and support prioritizing vaccination strategies for individuals with advanced immunosuppression. Full article

Background/Objectives: This study evaluated the Omicron LP.8.1 variant-adapted BNT162b2 mRNA vaccine (LP.8.1-adapted BNT162b2). Methods: This analysis is part of an ongoing phase 3 open-label study evaluating the immunogenicity, safety, and tolerability of LP.8.1-adapted BNT162b2. Reported here are descriptive 2-week post-vaccination results in 18–64 -year-olds at high risk of severe COVID-19 and in ≥65-year-olds who received the Omicron KP.2-adapted COVID-19 vaccine ≥ 6 months previously. Primary immunogenicity endpoints included neutralizing antibody geometric mean titers (GMTs) against LP.8.1 and KP.2 at 2 weeks after vaccination and geometric mean fold rises from baseline to 2 weeks after vaccination. Results were compared with a historical control group of adults who received KP.2-adapted BNT162b2 in a previous study. Tolerability and safety were also assessed. Results: Overall, 104 participants received LP.8.1-adapted BNT162b2 (18–64-year-olds, n = 51; ≥65-year-olds, n = 53). Baseline neutralizing GMTs were higher in LP.8.1-adapted BNT162b2 recipients than in the historical control group of KP.2-adapted BNT162b2 recipients against both sublineages (248 vs. 157 against LP.8.1; 372 vs. 187 against KP.2). Serum-neutralizing LP.8.1 and KP.2 GMTs increased 2 weeks after vaccination with LP.8.1-adapted BNT162b2 (1752 against LP.8.1; 2104 against KP.2) and historical control groups (1555 and 2395, respectively), and across both age groups. Reactogenicity events with LP.8.1-adapted BNT162b2 were generally mild or moderate and occurred at generally similar frequencies in both age groups. Adverse events were reported in 4.8% of participants (all in 18–64-year-olds); no serious adverse events were reported. Conclusions: After 2 weeks of follow-up, and in a small sample size, LP.8.1-adapted BNT162b2 was immunogenic in ≥65-year-olds and ≥18-year-olds at high risk of severe COVID-19. The safety and tolerability profile for LP.8.1-adapted BNT162b2 was consistent with the current US prescribing information for BNT162b2 and that of other variant-adapted BNT162b2 vaccines (Clinicaltrials.gov Identifier: NCT07069309, registered 16 July 2025). Full article

Background/Objectives: Our previous study demonstrated that while the third SARS-CoV-2 booster effectively enhanced immunity against the Delta subvariant, its protection declined over time. This study aimed to evaluate and compare the humoral and cellular immune responses, as well as reactogenicity, of the mRNA-1273 vaccine administered as a fourth booster in healthy Thai adults previously vaccinated with two doses of CoronaVac (CV) followed by a third dose of either AZD1222 (AZ) or BNT162b2 (BNT). Methods: Participants received a single 100 µg (0.5 mL) intramuscular dose of mRNA-1273. Blood samples were collected at baseline (D0), D14, D90, and D180 to assess anti-RBD IgG, conduct a surrogate virus neutralization test (sVNT) against the Delta and Omicron variants, and assess IFN-γ levels and reactogenicity. Results: Both 2CV/AZ- and 2CV/BNT-primed groups exhibited comparable local and systemic reactogenicity. The fourth mRNA-1273 dose markedly increased Delta variant inhibition within 14 days in both groups and remained at high levels at Days 90 and 180. sVNT inhibition against Omicron rose similarly in both groups at Day 14; it declined sharply by Days 90 and 180, with the 2CV/AZ-primed group showing significantly lower levels than the 2CV/BNT-primed group. Baseline anti-RBD IgG levels were lower in the 2CV/AZ group (p = 0.003) but surpassed those of the 2CV/BNT group by Day 14, with no significant differences at later time points. IFN-γ responses followed a similar pattern to anti-RBD IgG Conclusions: A heterologous fourth mRNA-1273 booster in both 2CV/AZ- and 2CV/BNT-primed groups effectively enhances B-cell and T-cell responses against SARS-CoV-2. However, emerging variants such as Omicron may still pose challenges. The trial was registered with the Thai Clinical Trials Registry: the name of the registry: “The comparison of immune response to the 4th dose booster with mRNA-1273 COVID-19 vaccine in individuals who had received 2 doses of CoronaVac and booster with ChAdOx-1 or BNT162b2 COVID-19 vaccine”, TCTR20220205002 on 5 February 2022. Full article

Background/Objectives: Understanding the relationship between reactogenicity and immunogenicity after repeated BNT162b2 vaccination is critical for optimizing vaccination strategies. This study quantified their progressive dissociation across four vaccine doses. Methods: We conducted a prospective longitudinal cohort study among Croatian healthcare workers vaccinated with BNT162b2 from January 2021 to January 2024. Anti-SARS-CoV-2 IgG antibodies were measured at 16 timepoints using chemiluminescent immunoassay. Local (pain, erythema, swelling) and systemic (fever, fatigue, headache, myalgia, arthralgia, nausea) reactions were recorded for 7 days using FDA toxicity scale. Correlations were analyzed with Spearman’s method and Bonferroni correction. Fourth-dose responses were predicted by exponential modeling. Results: Of 631 participants, 524 completed primary immunization, 418 received a third dose (173 with complete data), and 56 received a fourth dose (22 with complete paired data). Local reactions declined from 82.4% after the first dose to 42.9% after the fourth (p < 0.001). Systemic reactions peaked at 44.8% after the second dose, then decreased to 26.0% after the third and 19.6% after the fourth. In contrast, median antibody levels rose from 9910 AU/mL after the primary series to 29,002 AU/mL after the third and 38,274 AU/mL after the fourth. Correlations between reactions and antibody titer progressively weakened: r = 0.37 (95% CI 0.29–0.44, p < 0.001) after the primary series, r = 0.08 (95% CI −0.07 to 0.23, p = 0.30) after the third, and r = 0.04 (95% CI −0.39 to 0.45, p = 0.86) after the fourth dose. Conclusions: Progressive dissociation between reactogenicity and immunogenicity was observed across four BNT162b2 doses. Booster doses maintain robust antibody responses despite reduced reactogenicity, reinforcing that minimal side effects are consistent with sustained humoral responses. Full article

Background/Objectives: Guillain–Barré syndrome (GBS) is a rare but serious immune-mediated neurological disorder monitored as an adverse event of special interest during the COVID-19 pandemic. This study aimed to estimate the incidence of GBS following COVID-19 vaccination and SARS-CoV-2 infection and to compare the risk by vaccine platform. Methods: We conducted a population-based retrospective cohort study using data from the Valencia Health System Integrated Database (Spain) between January 2018 and March 2022. Two cohorts were defined: individuals receiving COVID-19 vaccines (mRNA-based vaccines (BNT162b2 [Pfizer–BioNTech] and mRNA-1273 [Moderna]) or non-virus-vectored (NVV) adenoviral vector-based vaccines (ChAdOx1-S [AstraZeneca] and Ad26.COV2.S [Janssen])) and individuals with laboratory-confirmed SARS-CoV-2 infection. Incident GBS cases were identified within a predefined 42-day risk window following vaccination or infection. Incidence rates were calculated per 100,000 vaccine doses administered or SARS-CoV-2 infections. Results: Among 5,109,919 individuals, 4,270,610 received at least one COVID-19 vaccine dose and 920,643 experienced at least one SARS-CoV-2 infection. A total of 69 GBS cases occurred within 42 days following vaccination (incidence: 0.67 per 100,000 doses), whereas 21 cases occurred after infection (incidence: 2.20 per 100,000 infections). Incidence was lower after mRNA-based vaccines (0.55 per 100,000 doses) than after NVV vaccines (1.57 per 100,000 doses). Conclusions: This study confirms that GBS occurrence following vaccination is rare. The incidence is lower among individuals who received mRNA vaccines compared to those who received NVV vaccines. Moreover, GBS appears to be more frequent after a COVID-19 infection than after vaccination. These findings highlight the importance of integrating pharmacoepidemiological analyses with pharmacovigilance data to contextualize rare but serious adverse events. Full article

COVID-19 mRNA vaccines activate type I interferon pathways and in genetically or immunologically predisposed individuals may trigger autoimmune responses, including autoantibodies against melanoma differentiation-associated protein 5 (MDA5). Although cases of dermatomyositis (DM), particularly anti-MDA5-positive DM, have been increasingly reported after SARS-CoV-2 vaccination, its clinical spectrum and management remain incompletely defined. We conducted a narrative review of the literature on post-vaccination dermatomyositis, focusing on clinical features, autoantibody profiles, therapeutic approaches, and outcomes. The review was enriched by the inclusion of a new case: a 60-year-old woman who developed anti-MDA5-positive dermatomyositis two weeks after receiving her fourth dose of the BNT162b2 (Pfizer/BioNTech) vaccine. She presented predominantly with cutaneous and articular manifestations in the absence of interstitial lung disease. Treatment with oral prednisone, intravenous alprostadil, and the Janus kinase inhibitor tofacitinib resulted in marked clinical improvement. This case, together with the literature review, illustrates both typical and atypical presentations of vaccine-associated anti-MDA5 DM, highlights diagnostic challenges without lung involvement, and suggests JAK inhibition as a potential therapeutic option, contributing to a more comprehensive understanding of post-vaccination dermatomyositis. Full article